Treatment of diarrhoea with compositions derived from carob pod

ABSTRACT

Diarrhoea is treated by administering particulated carob pod to a patient having diarrhoea wherein the particulated carob pod contains at least 20% by weight, based upon dry matter, of water-insoluble tannins expressed as total polyphenols and wherein the ratio by weight of water-soluble tannins to water-insoluble tannins is below 0.37 as determined in water at 37° C.

CROSS REFERENCE TO RELATED APPLICATION

This is a continuation application of Application Ser. No. 06/892,939filed Aug. 4, 1986, now U.S. Pat. No. 4,999,197.

BACKGROUND OF THE INVENTION

This invention relates to a dietetic product with depurative andanti-diarrhoeic activity.

Diarrhoeic illnesses, which are very common, constitute a very importantfactor in infantile and even adult mortality. Diarrhoea consists of avery frequent and very rapid passage of unformed stools and ischaracterized by the elimination of an excess of water in the stools,leading progressively to dehydration. This phenomenon appears to becaused by malabsorption, by excessive secretion or even by a deficiencyin intestinal motility; and these deficiencies may be concomitant.Although diarrhoea has several causes, it is accepted that the principalorigin is the presence of bacterial or viral toxins in the intestinaltract.

In simple terms, diarrhoea is at present treated with products whichabsorb water, toxins, viruses or bacteria by a physical phenomenon orwith medicaments which stimulate absorption, inhibit secretion or modifyintestinal motility or even antibiotics or even with rehydrationsolutions containing water and mineral salts which are administeredorally or intravenously.

The medicaments have the disadvantage that they are not always effectiveand produce side effects. Products which absorb water, for example gums,pectins, methyl cellulose, or carrots, may modify the frequency andconsistency of the stools, but do not reduce the losses of water andelectrolytes. Although rehydration solutions enable these losses to becompensated, they attenuate the effects of the diarrhoea instead ofattacking its causes. Products capable of absorbing toxins, viruses andbacteria, for example calcium carbonate, hydrated aluminium silicate,bismuth salts, pectins, or active carbon, are very popular, but it isnot certain whether they are really effective. Ion exchange resins,which additionally have the property of fixing the bile salts, appear tobe effective, but also produce side effects and have to be used in highdoses.

A dietetic composition containing from 60 to 80% roasted carob flour iscommercially available (AROBON). Although this product gives goodresults in the treatment of diarrhoea without producing side effects, ithas the disadvantage of necessitating relatively high doses, of theorder of 20-40 g/day for young children, which presents problems ofadministration.

SUMMARY OF THE INVENTION

The present invention provides a dietetic product which is active in thetreatment of diarrhoea without having any of the disadvantages mentionedabove.

The dietetic product according to the invention is characterized in thatit comprises as an active principle a carob flour containing at least20% by weight, based on dry matter, of native tannins, expressed astotal polyphenols, of which the ratio by weight of soluble tannins toinsoluble tannins is below 0.37, solubility being determined in water at37° C.

The present invention also relates to a process for the preparation ofcarob flour characterized in that ripe carob pods are treated with anaqueous medium to extract most of the sugars and water-soluble tannins,the residue is separated, dried under conditions which avoid thermaldenaturing of the water-in-soluble tannins present in the residue, i.e.,at a temperature not exceeding 100° C., and then ground into particlessmaller than or equal to 200 μm in diameter.

In the context of the invention, native tannins are understood to betannins which have not been denatured by a heat or chemical treatment.For example, when non-desugared or partially desugared carob pods"(Ceratonia siliqua)" are roasted, a Maillard reaction takes place whichdestroys the structure of the tannins, as reflected in the fact that thecrystals characteristic of condensed carob tannins are no longer visibleunder a microscope. Similarly, if , for example, carob is treated withacids, the tannins are converted into phlobaphenes by polymerization.

In ripe carob, the majority of tannins are present in condensed form,i.e., in the form of polymers consisting of sub-units of 3-flavanol andgallic esters thereof. These tannins are insoluble in cold or tepidwater and particularly at body temperature, i.e., at 37° C. The resultof this is that they arrive in the intestine without having beendegraded by gastric acid or inactivated by proteins. Accordingly, theyare able to perform their depurative and antiseptic function withoutintervening in the physiological processes.

The tannin content may be evaluated by determining the totalpolyphenols, for example by applying a modified version of thecolorimetric method of Folin-Denis, "Tannin" in Official Methods ofAnalysis (1980), W. Horwitz, ed., Association of Official AnalyticalChemists, Washington D.C. This modified method comprises initiallydetermining the soluble tannins, extracted with water at 37° C. whilestirring moderately for 15 mins., in the supernatant liquid obtainedafter decantation. This is followed by determination of the condensedtannins which are insoluble in water at 37° C. and which are extractedfrom the solid phase with dimethyl formamide at 120° C. over a period of4 h with intermittent stirring every 20 mins. The tannins may also bedetermined by gravimetry using the method described by L. Vuataz, H.Branderberger and R. Egli in J. Chromatogr. (1959), Vol. 2, pp. 173-187.

The carob flour is preferably enriched with tannins in relation to theripe carob pod. Advantageously, it contains from 30 to 90% by weight,based on dry matter, of tannins expressed as total polyphenols. Amongthese tannins, the solubles advantageously represent less than 10% andpreferably less than 6% by weight, for example approximately 4% byweight. The ratio by weight of soluble tannins to insoluble tannins isthus preferably from 0.04 to 0.1.

The dietetic product according to the invention may be presented in anyform suitable for oral administration. Thus, it may be formulated as apowder for dispersion in an aqueous medium, for example water, milk, afruit juice, or an isotonic beverage. In addition to carob flour, apowder such as this will advantageously contain permitted foodadditives, for example effervescent agents, for example a mixture ofacid and carbonate, wetting agents, for example lecithin, flavourings,rehydration salts, or peptides emanating, for example, from hydrolyzedproteins. It may also contain sugars, advantageously maltodextrin,dextrose or preferably sucrose, for example, in the quantity necessaryto standardize the percentage by weight of tannins, expressed as totalpolyphenols, of the preparation to a predetermined value, preferably ofthe order of 22% by weight.

Alternatively, the dietetic product may be presented in the form ofoptionally effervescent granulates, tablets or dragees for chewing ordissolving prepared from the flour by standard methods.

Finally, the dietetic product may be presented as a food, advantageouslya dessert, for example a cream, a jelly or a baked custard in which thecarob flour is incorporated.

The quantity administered will of course depend upon the age of thepatient (infant, child or adult), upon the nature and gravity of thediarrhoea to be treated and upon the nature of the treatment itself(preventive or curative). For instance, a dose comprising 1-2 g carobflour/kg body weight/day and preferably 1 g/kg/day up to 10 kg bodyweight and up to 20 g/day beyond 10 kg body weight enables the diarrhoeato be treated in 8 to 10 days. The flour may be dispersed in an aqueousmedium in a quantity of from 1 to 3% by weight.

The flour may be packed, preferably in an inert atmosphere, for examplein 100 g boxes with a measuring spoon or in sachets of 5-10 g which areimpermeable to air, light and moisture.

The above carob flour shows bactericidal activity on enteropathogenic"Staphylococcus aureus" and "E. coli" and bacteriostatic activity on E.coli. Its inhibiting effect is probably due to the mechanical adsorptionof the bacteria onto the granules of tannins which it contains and tothe progressive release of the soluble tannins from those granules. Ithas also been found that the granules of tannins in question adsorb theenterotoxin of cholera and the thermolabile enterotoxin of E. coli andthat they inactivate the enteroviruses. In the doses in which they aretaken, these tannins do not affect the normal process of digestiondespite the antinutritional activity which they are known to showthrough inhibition of the digestive enzymes. They have a detoxificatingeffect and a delayed action and are not absorbed in contrast to theantibiotics normally prescribed.

The ripe carob pods used as starting material are characterized by apercentage sugar content which has reached the maximum through ripening,i.e., approximately 50% by weight, of which approximately 40% by weightis sucrose, and by a moisture content of less than 20% by weight. Theyare preferably crushed into fragments smaller than 1.5 cm in diameter,if necessary after having been frozen. The carob without the seeds thushas the following standard composition:

    ______________________________________                                                               % by weight of                                                                dry matter                                             ______________________________________                                        Soluble carbohydrates    49                                                   Soluble polyphenols      1.2                                                  Insoluble tannins (determined by gravimetry)                                                           19.8                                                 incl. polyphenols        (11)                                                 Pectin, hemicellulose-lignocellulose                                                                   24.5                                                 Proteins (N × 6.25)                                                                              3                                                    Ash                      2.5                                                  ______________________________________                                    

In a first continuous embodiment of the process, which is preferred, thecarob is ground in the presence of cold water, for example at 15° to 20°C., for example in a colloid mill. The quantity of water added ispreferably from 5 to 15 times the quantity of carob. After separation ofthe liquid phase, for example in a decanter, the desugared carob iscollected.

The desugared carob is preferably heat-treated, for example by additionof an equivalent quantity by weight of hot water, after which thedispersion is pasteurized, for example by the direct injection of steamat 95°-98° C. for 30 s to 10 mins. This heat treatment has the advantageof removing most of the microorganisms from the dispersion before it issubsequently ground.

The pasteurized dispersion is then ground, preferably first in a toothedmill and then in an edge mill at a temperature not exceeding about 90°C. The dispersion is then dried, preferably by spraying into a tower.Drying takes place under conditions which avoid thermal denaturing ofthe tannins, i.e., at a temperature not exceeding 100° C. and preferablyat a temperature of 90° C. at the level of the product.

Finally, the powder obtained is dry-ground, for example in a pinned-discmill, to give a flour of which the particles have a diameter of lessthan or equal to 200 μm, advantageously from 10 to 200 μm and preferablyof the order of 100 μm, which ensures that no unpleasant granularity canbe detected in the dietetic product containing the flour and avoidsrapid sedimentation of the particles, for example in a beverage.

In a second embodiment of the process, which is carried out in batches,the crushed carob, preferably in the form of particles 0.8 to 5 mm indiameter, is introduced into hot water, preferably at 60° to 98° C.Columns may be filled with the crushed carob and water subsequentlypassed through the columns thus filled or, alternatively, the crushedcarob may be suspended in water in tanks and the suspension stirred. Thesolid phase is then collected, for example by gravity or by decantation,and dried in hot air. For example, the moist residue may be placed onshelves in a dryer, in which preferably a partial vacuum and atemperature of from 60° to 70° C. prevail, and left there for 24 to 72h. Finally, the dried material is ground, for example in a pinned-discmill, to give particles from 10 to 200 μm in diameter and preferablyaround 100 μm in diameter.

In a variant of the embodiments described above, which enables the flourto be enriched with tannins, the dispersion or the residue may be dried,for example by freeze drying, converted into granules, for example bymeans of a granulation plate, and the granules thus formed crushed, forexample in an edge mill or in a cylinder mill, and most of the fineseliminated, for example by elutriation in a stream of hot air.

The particles obtained preferably have diameters of from 10 to 200 μm.

EXAMPLES

The invention is illustrated by the following Examples in which thepercentages represent percentages by weight, unless otherwise indicated.

EXAMPLE 1

1.7 kg/min of ripe deseeded carob pods crushed into particles having anaverage diameter of 2 cm and having a dry matter content of 95% arecontinuously introduced into a colloid mill in the presence of 21 l/minrunning water at 18° C., the dispersion being removed through a sievehaving a mesh width of 1 mm. After a dwell time of 6 mins., thedispersion is introduced into a decanter in which the liquid phase isseparated and the solid phase containing 18% of fibres, expressed as drymatter, is collected.

After the solid phase has been mixed with as much running water at 95°C., the dispersion is pasteurized by direct injection of steam at95°-97° C. for 30 s and then ground at 85° C. first in a toothed milland then in an edge mill. The ground dispersion is then dried byspraying into a tower at 175 l/h, the entry air temperature being from165° to 170° C. and the exit air temperature from 96° to 98° C. Underthese conditions, the temperature at the level of the product does notexceed 90° C. Finally, the powder is dry-ground in a pinned-disc millrotating at 9000 r.p.m.

The particles obtained have a dry matter content of 3%. 50% pass througha 75 μm mesh screen and 100% through a 200 μm mesh screen.

The flour has the following composition, expressed as dry matter:

    ______________________________________                                                         %                                                            ______________________________________                                        Soluble carbohydrates                                                                            19.3                                                       Tannins (gravimetry)                                                                             47.4                                                       incl. polyphenols  (27)                                                       Fibres             25.7                                                       Proteins           4.8                                                        Ash                2.8                                                        ______________________________________                                    

The ratio of soluble tannins to insoluble tannins is 0.23:1.

EXAMPLE 2

127 kg of deseeded crushed ripe carob pods having a dry matter contentof 89% are frozen at -40° C., size-reduced in a cutter with an openingof 3 mm and the fines subsequently eliminated through a 0.8 mm meshscreen. The remaining 108 kg are introduced into columns. After theparticles have been swollen in deionized water, deionized water at 70°C. is passed through the columns at a rate of 180 l/h. After the columnshave been drained by gravity, 210 kg of solid particles having a drymatter content of 19% are collected. The wet particles are placed onshelves in an air dryer and dried for 48 h at an air temperature of 80°C. and under a pressure of 60 mb. 42.5 kg of dried material having a drymatter content of 89.5% are thus obtained. Finally, this material isground at a rate of 40 kg/h in a pinned-disc mill rotating at 12,000r.p.m. which gives 40 kg of flour of which the particles have a drymatter content of 92% and an average diameter of 100 μm.

The flour has the following composition, expressed as dry matter:

    ______________________________________                                                         %                                                            ______________________________________                                        Soluble carbohydrates                                                                            22.5                                                       Tannins (gravimetry)                                                                             36.2                                                       incl. polyphenols  (22.6)                                                     Fibres             34.9                                                       Proteins           4.6                                                        Ash                1.8                                                        ______________________________________                                    

The ratio of soluble tannins to insoluble tannins is 0.06:1.

EXAMPLE 3

29 kg of ripe carob pods which have been stored for at least 6 months,deseeded, crushed and ground into particles having an average diameterof 5 mm are treated with 100 kg deionized water at 98° C. in a tank withstirring for a period of 10 minutes. The dispersion is then centrifuged,34.5 kg of residue are collected and are then washed for 10 mins. at 15°C. with 100 kg deionized water. After the dispersion has beenre-centrifuged, 27.2 kg of residue are collected and are then dried byfreeze drying. After granulation into particles having an averagediameter of 3 mm on a granulation plate, the particles are crushed in acylinder mill and the fibres are eliminated by a stream of hot air.Final grinding in a micronizer gives a flour which is enriched withinsoluble tannins in relation to the starting carob and of which theparticles have an average diameter of 25 μm.

The flour has the following composition, expressed as dry matter:

    ______________________________________                                                             %                                                        ______________________________________                                        Soluble carbohydrates  --                                                     Tannins (gravimetry)   71.7                                                   incl. polyphenols      (41.9)                                                 Fibres                 22.6                                                   Proteins and ash        5.7                                                   ______________________________________                                    

The ratio of the soluble tannins to the insoluble tannins is 0.04:1.

EXAMPLE 4

82% carob flour prepared in accordance with Example 1 are dry-mixed for30 mins. with 17.9% finely ground sucrose containing 3% soya lecithinand 0.1% vanillin and the resulting mixture is ground in a mill having a0.8 mm mesh sieve. The powder is then packed together with a measuringspoon in 160 g boxes which are impermeable to light, air and moisture.

EXAMPLE 5 Effervescent Granulates

Premix I

80 g gelatin, 2 kg carob flour prepared in accordance with Example 1 and160 g maltodextrin having a dextrose equivalent of 5% are dry-mixed.

4 liters cold deionized water are added to this mixture in a kneader andthe whole is homogeneously mixed. The paste is then dried for 12 h at40°-50° C. in a shelf dryer.

Premix II

An effervescent premix containing 25% citric acid, 52.3% sodiumbicarbonate and 22.7% tartaric acid is prepared, after which 21.6 gpowder-form vegetable wax, 4.8 g magnesium stearate and 50.4 g orangeflavouring are added to 75.2 g of this premix.

Premixes I and II are thoroughly mixed and then ground into granulateshaving an average diameter of 1.5 mm.

EXAMPLE 6 Effervescent Tablets

Effervescent tablets weighing 0.65 g for a diameter of 1 cm and athickness of 7.2 mm are prepared from the granulates obtained inaccordance with Example 5 by compressing the granulates in a cylindricalchamber 1 cm in diameter and 16 mm deep.

EXAMPLE 7 Chewing Tablets

Chewing tablets are prepared from the following ingredients:

    ______________________________________                                                          %                                                           ______________________________________                                        Carob flour of Example 1                                                                          81.4                                                      Corn protein        7.1                                                       Edible fat          3.4                                                       Mint flavouring     1.5                                                       Maltodextrin        6.2                                                       Calcium stearate    0.4                                                       ______________________________________                                    

The various ingredients are dry-mixed and then compressed as in Example6.

EXAMPLE 8 Chewing Granulates

After dry-mixing of the following ingredients:

    ______________________________________                                                          %                                                           ______________________________________                                        Carob flour of Example 1                                                                          80                                                        Malt extract        10                                                        Cocoa butter        10                                                        ______________________________________                                    

granulates are prepared using a compactor comprising hollow toothedwheels drilled with holes 2-3 mm in diameter. Scrapers placed inside thewheels cut the strands issuing from the holes into granulates which arethen coated with a film of gum arabic and sprayed with a flavoured sugarsyrup.

EXAMPLE 9 Flavoured Milk

A flavoured milk is prepared by mixing 15 g whole-milk powder containing50% sucrose with 6 g of the flour of Example 1 and traces of strawberryflavouring.

A beverage is obtained by diluting this mixture in 100 ml water.

EXAMPLE 10

Cream

A chocolate-flavoured cream is prepared from 50 g of a powder-formchocolate cream mix to which 12 g of the carob flour of Example 1 areadded, the whole then being diluted in 100 ml cold milk. The creamobtained is homogeneous and the presence of the carob flour is notnoticeable.

EXAMPLE 11 Powder For Oral Rehydration

The following ingredients are dry-mixed in the quantities indicated:

    ______________________________________                                        Potassium chloride     1.5     g                                              Sodium chloride        3.5     g                                              Sodium hydrogen carbonate                                                                            2.5     g                                              Glucose monohydrate    20      g                                              Flour of Example 1     10-15   g                                              ______________________________________                                    

At the moment of use, this mixture is diluted in 1 liter running waterpreferably sterilized beforehand. The volume of liquid to be ingestedfor children is 50-100 ml/kg body weight/4h and up to 750 ml/h foradults, the quantity of flour ingested per day not exceeding 20 g.

EXAMPLE 12

The effect of the flour obtained in accordance with Example 1 on acutediarrhoea (6-12 stools/day) in children caused predominantly by "E.coli" was studied. 33 children aged between 5 and 30 months were given 1g carob flour per kg body weight mixed with porridge. In 28 cases (85%),the diarrhoea was stopped in 48-72 h.

Another group of 31 children aged between 1 and 12 months suffering fromacute diarrhoea (more than 5 stools/day) was given 5 g per kg bodyweight and at most 40 g/day of commercial roasted carob flour (AROBON)in a milk in a quantity of 5%. 26 cases (84%) were cured in 7 days.

Another comparison group treated with an antibiotic, namelychloramphenicol, showed 64% recovery after 7 days.

It can thus be seen that the carob flour prepared in accordance with theinvention is more active in a 5 times smaller dose than the roastedcarob flour and a widely prescribed antibiotic without having any of thedisadvantages of the antibiotic (side effects, deterioration of theintestinal flora).

I claim:
 1. A method for treating diarrhoea comprising administering acomposition to a patient having diarrhoea comprising particulated carobpod wherein the particulated carob pod contains at least 20% by weight,based upon dry matter, of water-insoluble tannins expressed as totalpolyphenols and wherein a ratio by weight of water-soluble tannins towater-insoluble tannins is below 0.37 as determined in water at 37° C.2. A method according to claim 1 wherein the particulate carob pod ofthe composition contains from 30% to 90% by weight of water-insolubletannins expressed as total polyphenols.
 3. A method according to claim 1wherein the patient is a human.
 4. A method according to claim 3 whereinthe composition is administered in an amount of from 1 g/kg to 2 g/kgbody weight/day.
 5. A method according to claim 3 wherein for bodyweights up to a body weight of 10 kg, the composition is administered inan amount of 1 g/kg/day.
 6. A method according to claim 3 wherein forbody weights in excess of 10 kg, the composition is administered in anamount of up to 20 g/day.
 7. A method according to claim 3 wherein theparticulated carob pod of the composition has a particle size of up to200 μm in diameter.
 8. A method for treating conditions in a patient dueto enteropathogenic organisms selected from organisms of the group oforganisms consisting of Staphylococcus aureus, E. coli, andenteroviruses comprising administering a composition comprisingparticulated carob pod wherein the particulated carob pod contains atleast 20% by weight, based upon dry matter, of water-insoluble tanninsexpressed as total polyphenols and wherein a ratio by weight ofwater-soluble tannins to water-insoluble tannins is below 0.37 asdetermined in water at 37° C.
 9. A method according to claim 8 whereinthe patient is a human.
 10. A method for the treating conditions due toenterotoxins in patients due to an enterotoxin selected from a group ofenterotoxins consisting of enterotoxins E. coli and cholera andenteroviruses comprising administering a composition comprisingparticulated carob pod wherein the particulated carob pod contains atleast 20% by weight, based upon dry matter, of water-soluble tanninsexpressed as total polyphenols and wherein a ratio by weight ofwater-soluble tannins to water-insoluble tannins is below 0.37 asdetermined in water at 37° C.
 11. A method according to claim 10 whereinthe patient is a human.